Population Pharmacokinetics and Dosing Considerations for Gentamicin in Newborns with Suspected or Proven Sepsis Caused by Gram-Negative Bacteria.

Aim To describe the population pharmacokinetics (PK) of gentamicin in neonates with suspected or proven gram-negative sepsis and determine the optimal dosage regimen in relation to the bacterial minimum inhibitory concentrations (MIC) found in this population. Methods Data were prospectively collected between October 2012 and January 2013 in the Neonatal Intensive Care unit (NICU) at the Academic Medical Centre (AMC), Amsterdam, The Netherlands. A single non-linear mixed-effects regression analysis (NONMEM®) was performed to describe the population PK of gentamicin. Dosage regimens based upon gestational age (GA) were generated using Monte Carlo simulations with the final model. Target values were based on the MIC distribution in our patient population. Results In total 136 gentamicin concentrations from 65 (pre)term neonates were included. The PK was best described by an allometric 2-compartment model with postmenstrual age (PMA) as a covariate on clearance (Cl). The MIC distribution (median 0.75 (range 0.5-1.5) mg/L) justified a gentamicin target peak concentration of 8-12 mg/l. Conclusion This study describes the PK of gentamicin in (pre)term neonates. A dosage regimen of 5 mg/kg every 48 hours, 5 mg/kg every 36 hours, and 5 mg/kg every 24 hours for patients with GA